{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:58:03Z","timestamp":1792432683329,"version":"4.5.0"},"reference-count":79,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T00:00:00Z","timestamp":1603497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007029","name":"Leonard Wood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007029","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma\/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti\u2010inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID\u201019). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.<\/jats:p>","DOI":"10.1002\/biof.1687","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T08:54:45Z","timestamp":1603529685000},"page":"190-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":218,"title":["Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-8681","authenticated-orcid":false,"given":"Duraisamy","family":"Kempuraj","sequence":"first","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramasamy","family":"Thangavel","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak D.","family":"Kempuraj","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"David H. Hickman High School Columbia Public Schools  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ejaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govindhasamy Pushpavathi","family":"Selvakumar","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhanshu P.","family":"Raikwar","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita A.","family":"Zaheer","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shankar S.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghav","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premkumar Nattanmai","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asgar","family":"Zaheer","sequence":"additional","affiliation":[{"name":"Department of Neurology School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"The Center for Translational Neuroscience School of Medicine, University of Missouri  Columbia Missouri USA"},{"name":"Harry S. Truman Memorial Veterans Hospital U.S. Department of Veterans Affairs  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24535"},{"issue":"6","key":"e_1_2_8_3_1","first-page":"134","article-title":"Brain injury\u2010mediated neuroinflammatory response and Alzheimer's disease","volume":"26","author":"Kempuraj D","year":"2019","journal-title":"Neuroscientist"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00054"},{"issue":"1","key":"e_1_2_8_5_1","first-page":"1003","article-title":"Neuroinflammation induces neurodegeneration","volume":"1","author":"Kempuraj D","year":"2016","journal-title":"J Neurol Neurosurg Spine"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.01.013"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071687"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000729"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00187"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2017-317557"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00395"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/02699052.2017.1312528"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0319-5"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.255958"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-011-0125-x"},{"issue":"4","key":"e_1_2_8_16_1","first-page":"86","article-title":"Current trends in biomarkers for traumatic brain injury","volume":"12","author":"Mehta T","year":"2020","journal-title":"Open Access J Neuro Neurosurg"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4243953"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9040297"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112754"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00225"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.09.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/CEJ.0000000000000128"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00692"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/diseases4030028"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)01304-0"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955709787001712"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118173"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-018-1094-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9030216"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSMBR.893093"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00171"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.549691"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8098439"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858416687249"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00216"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000991"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-25"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-020-03058-3"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2018.1504961"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.356"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463201002300406"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2019.07.005"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2014.3460"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0229-z"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01551"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.248519"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120913094"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22714"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01245-6"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026617666181119154247"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.47162\/RJME.61.1.07"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1633"},{"issue":"3","key":"e_1_2_8_53_1","article-title":"Dexamethasone for COVID\u201019? Not so fast","volume":"34","author":"Theoharides TC","year":"2020","journal-title":"J Biol Regul Homeost Agents"},{"issue":"3","key":"e_1_2_8_54_1","first-page":"767","article-title":"SARS\u2010CoV\u20102, which induces COVID\u201019, causes Kawasaki\u2010like disease in children: Role of pro\u2010inflammatory and anti\u2010inflammatory cytokines","volume":"34","author":"Ronconi G","year":"2020","journal-title":"J Biol Regul Homeost Agents"},{"issue":"4","key":"e_1_2_8_55_1","first-page":"955","article-title":"Luteolin inhibits mast cell\u2010mediated allergic inflammation","volume":"27","author":"Kritas SK","year":"2013","journal-title":"J Biol Regul Homeost Agents"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-72005-0_45"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707668"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1524845114"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172760"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2019.1690480"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.obmed.2020.100281"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.104146"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109211"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858420941476"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370213477985"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-018-2482-2"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-015-0440-8"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91680-6"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0822-1"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.02.003"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-020-03108-w"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110044"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-016-8430-x"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2017.05.014"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200443"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15010895"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.07.042"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.03.009"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.10.046"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-211-73574-9_9"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.1687","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.1687","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.1687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T03:26:15Z","timestamp":1693538775000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.1687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,24]]},"references-count":79,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/biof.1687"],"URL":"https:\/\/doi.org\/10.1002\/biof.1687","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,24]]},"assertion":[{"value":"2020-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}